Detection, Mapping, and Proteotyping of SARS-CoV-2 Coronavirus with High Resolution Mass Spectrometry

A high resolution mass spectrometry approach has been applied for the first time to detect and characterize SARS-CoV-2 coronavirus in cell cultured and nasopharyngeal swab specimens. Peptide ions for three of the most abundant structural viral proteins (membrane, nucleocapid, and spike) are detected and assigned directly, by virtue of the high resolution and mass accuracy within the mass maps of whole virus digests, without the need for tandem mass spectrometry (MS/MS). MALDI-MS based approaches offer high sample throughput and speed, compared with those of LC-MS strategies, and detection limits at some 10⁵ copies, or orders of magnitude less with selected ion monitoring, that compete favorably with conventional reverse transcription polymerase chain reaction (RT-PCR) strategies. The detection of signature peptides unique to SARS-CoV-2 coronavirus over those from the influenza virus allows for its unambiguous detection.